title: Modulating role of dopamine on anesthetic requirements.
abstract: The influence of dopamine on halothane anesthetic requirements was determined in mice. Halothane anesthetic requirement was defined as the minimum anesthetic concentration (MAC) that prevented 50% animals from moving in response to a supramaximal stimulus. Levodopa (L-DOPA) dose-dependently decreased halothane MAC to a maximum of 49% of control; over the same dose range L-DOPA increased striatal dopamine nearly 4-fold. The MAC-reducing effect of L-DOPA was attenuated by selective antagonism of the D2 dopamine receptor with YM-09151-2 while selective blockade of the D1 dopamine receptor with SCH-23390 did not alter L-DOPA's effect on the MAC for halothane. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) decreased striatal dopamine by 82% and increased the MAC for halothane by 27%. Repletion of striatal dopamine with L-DOPA, in MPTP-treated mice, restored the MAC for halothane back to the control state. The regression line derived from the plot of halothane MAC versus striatal dopamine content shows a highly significant correlation between the two variables (r2 = 0.94). These are the first results to suggest that anesthetic requirements can be modulated directly and precisely by increasing or decreasing the content of a single neurotransmitter in the central nervous system.
authors.affiliation: Department Anesthesia, Stanford University, CA 94305.
authors.forename: I S
authors.initials: IS
authors.lastname: Segal
authors.forename: J K
authors.initials: JK
authors.lastname: Walton
authors.forename: I
authors.initials: I
authors.lastname: Irwin
authors.forename: L E
authors.initials: LE
authors.lastname: DeLanney
authors.forename: G A
authors.initials: GA
authors.lastname: Ricaurte
authors.forename: J W
authors.initials: JW
authors.lastname: Langston
authors.forename: M
authors.initials: M
authors.lastname: Maze
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002230:Carbidopa / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006221:Halothane; D007700:Kinetics; D007980:Levodopa / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011954:Receptors, Dopamine / Q000187:drug effects
chemical_list: D001549:Benzamides; D001552:Benzazepines; D011954:Receptors, Dopamine; C048977:1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002230:Carbidopa; C030265:nemonapride; D006221:Halothane; D004298:Dopamine